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Most recently, the adenosine is considered as one of the most promising targets for treating pain, with few side effects. It exists in the central nervous system, and plays a key role in nociceptive afferent pathway. It is reported that the A1 receptor (A1R) could inhibit Ca²⁺ channels to reduce the pain like analgesic mechanism of morphine. And, A...
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... Other interactions via conventional hydrogen bonds at the active site were TYR 118, LEU 110, and SER 112. When the native and redocked PGE was superimposed, an RMSD generated by Pymol was 1.067, an RMSD of ≤2 is generally preferred for higher accuracy of docking (Xu et al., 2021). The redocked and RMSD outputs give validity to the docking protocol. ...
... Beyond the topic of purinergic signalling in acupuncture, pain is another main concern of this collection. Molecular docking strategies and molecular dynamics simulations were applied to identify six potential small molecules as A 1 agonists and/or A 2A antagonists, which can improve pain [21]. The mechanism of P2X3R-mediated pain in streptozocin-induced diabetic neuropathy [22], P2X4R-mediated visceral hypersensitivity after neonatal maternal separation in untreated rats [23], or in diabetic neuropathic pain and depressive-like behavior in type 2 diabetic rats [24] are also subjects of these investigations. ...
... In fact, all of the target proteins had key interactions with karanjin. The interactions are similar to previous works of research with docking results of other bioactive substances with A2A [58,59], ASN [60,61], MAO-B [62][63][64] and COMT [65][66][67]. ...
Parkinson’s disease (PD) and Alzheimer’s disease (AD) are neurodegenerative disorders that have emerged as among the serious health problems of the 21st century. The medications currently available to treat AD and PD have limited efficacy and are associated with side effects. Natural products are one of the most vital and conservative sources of medicines for treating neurological problems. Karanjin is a furanoflavonoid, isolated mainly from Pongamia pinnata with several medicinal plants, and has been reported for numerous health benefits. However, the effect of karanjin on AD and PD has not yet been systematically investigated. To evaluate the neuroprotective effect of karanjin, extensive in silico studies starting with molecular docking against five putative targets for AD and four targets for PD were conducted. The findings were compared with three standard drugs using Auto Dock 4.1 and Molegro Virtual Docker software. Additionally, the physiochemical properties (Lipinski rule of five), drug-likeness and parameters including absorption, distribution, metabolism, elimination and toxicity (ADMET) profiles of karanjin were also studied. The molecular dynamics (MD) simulations were performed with two selective karanjin docking complexes to analyze the dynamic behaviors and binding free energy at 100 ns time scale. In addition, frontier molecular orbitals (FMOs) and density-functional theory (DFT) were also investigated from computational quantum mechanism perspectives using the Avogadro-ORCA 1.2.0 platform. Karanjin complies with all five of Lipinski’s drug-likeness rules with suitable ADMET profiles for therapeutic use. The docking scores (kcal/mol) showed comparatively higher potency against AD and PD associated targets than currently used standard drugs. Overall, the potential binding affinity from molecular docking, static thermodynamics feature from MD-simulation and other multiparametric drug-ability profiles suggest that karanjin could be considered as a suitable therapeutic lead for AD and PD treatment. Furthermore, the present results were strongly correlated with the earlier study on karanjin in an Alzheimer’s animal model. However, necessary in vivo studies, clinical trials, bioavailability, permeability and safe dose administration, etc. must be required to use karanjin as a potential drug against AD and PD treatment, where the in silico results are more helpful to accelerate the drug development.
